Cardiovascular Diseases Genetic Testing Program Description: Congenital Heart Disease Panels We offer comprehensive gene panels designed to • Congenital Heart Disease Panel (187 genes) diagnose the most common genetic causes of hereditary • Heterotaxy Panel (114 genes) cardiovascular diseases. Testing is available for congenital • RASopathy/Noonan Spectrum Disorders Panel heart malformation, cardiomyopathy, arrythmia, thoracic (31 genes) aortic aneurysm, pulmonary arterial hypertension, Marfan Other Panels syndrome, and RASopathy/Noonan spectrum disorders. • Pulmonary Arterial Hypertension (PAH) Panel Hereditary cardiovascular disease is caused by variants in (20 genes) many different genes, and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Other Indications: than condition-specific panels, we also offer single gene Panels: sequencing for any gene on the panels, targeted variant • Confirmation of genetic diagnosis in a patient with analysis, and targeted deletion/duplication analysis. a clinical diagnosis of cardiovascular disease Tests Offered: • Carrier or pre-symptomatic diagnosis identification Arrythmia Panels in individuals with a family history of cardiovascular • Comprehensive Arrhythmia Panel (81 genes) disease of unknown genetic basis • Atrial Fibrillation (A Fib) Panel (28 genes) Gene Specific Sequencing: • Atrioventricular Block (AV Block) Panel (7 genes) • Confirmation of genetic diagnosis in a patient with • Brugada Syndrome Panel (21 genes) cardiovascular disease and in whom a specific gene • Catecholaminergic Polymorphic Ventricular Tachycardia associated diagnosis is suspected (CPVT) Panel (11 genes) Variant Specific Analysis: • Long QT Syndrome Panel (19 genes) • Pre-symptomatic testing of at-risk siblings and parents for medical management • Short QT Syndrome Panel (6 genes) • Carrier identification in individuals in whom specific Connective Tissue Disorders Panel variant(s) have been identified in the proband • Thoracic Aortic Aneurysm Panel (49 genes) • Prenatal diagnosis of an at-risk fetus, after • Marfan Syndrome and MFS Related Disorders Panel confirmation of variant(s) in the parent(s) and by (3 genes) prior arrangement only Cardiomyopathy Panels Deletion/Duplication Analysis: • Comprehensive Cardiomyopathy Panel (135 genes) • Completion of the diagnostic evaluation in a patient • Arrhythmogenic Right Ventricular Cardiomyopathy with a clinical diagnosis of cardiovascular disease (ARVC) Panel (18 genes) who has had a negative panel or who is heterozygous • Dilated Cardiomyopathy (DCM) Panel (73 genes) for a variant in a gene associated with an autosomal • Hypertrophic Cardiomyopathy (HCM) Panel (98 genes) recessive condition. • Left Ventricular Noncompaction (LVNC) Panel (36 genes) • Restrictive Cardiomyopathy (RCM) Panel (9 genes) Laboratory of Genetics and Genomics CLIA#: 36D0656333 Phone: (513) 636-4474 Fax: (513) 636-4373 Email: [email protected] www.cincinnatichildrens.org/genetics Specimen: Test Sensitivity: Provide at least 3 mL of whole blood in a lavender top Analytical Sensitivity: The sensitivity of DNA sequencing (EDTA) tube or saliva in an Oragene saliva kit. Please call is over 99% for the detection of nucleotide base changes, the lab at 513-636-4474 for a free saliva collection kit. small deletions and insertions in the regions analyzed. Label the tube with the patient’s name, birth date, and Sequencing Test Limitations: Pathogenic variants may date of collection. Alternatively, 10 mcg of high quality be present in a portion of the genes not covered by this DNA may be submitted. test or in regions with suboptimal data due to For prenatal samples, at least 20 mL of amniotic fluid or at homologous issue, polynucleotides, or nucleotide least 30 mg chorionic villi or 2 flasks of cultured cells is repeats, and therefore may not be identified. Thus, the needed. 3 mL of maternal blood in lavender top (EDTA) absence of identified pathogenic variants does not tube is needed for maternal cell contamination studies. exclude the possibility of a genetic etiology for the patient’s symptoms.•Certain types of mutations are not Testing Methodology: detected. Only single base pair changes or small Panels: Our panels utilize Exome Sequencing (ES) insertions or deletions of DNA are detected. Large technology to detect variants in predefined lists of deletions, duplications, or rearrangements, clinically relevant genes to identify inherited forms of mitochondrial genome mutations, repeat expansions, cardiovascular diseases. Our panels use the Human low level mosaicism and many epigenetic defects may Comprehensive Exome kit from Twist Bioscience to not be detected by this test. capture the exonic regions of genes from the genomic Regions of Homology DNA extracted from the patient. Targeted regions are These gene regions with homology may generate sequenced using the Illumina sequencing system with suboptimal data with potential false negative results. paired-end reads. Sequence reads are aligned to reference TRANSCRIPT genome (build UCSC hg19). Variants within exons and GENE EXON CHROM EXON_START EXON_END ARMC4 NM_001290020 9 10 28257851 28257947 flanking sequences are identified and evaluated by a CDC42 NM_001791 6 1 22417920 22418010 validated in-house developed bioinformatics analysis FLNC NM_001458 47 7 128498061 128498271 pipeline and Fabric software packages. Data quality is LEFTY2 NM_001172425 3 1 226127455 226127571 assessed to confirm it has a minimum coverage of 20X for SDHA NM_004168 14 5 254507 254621 >95% of targets of interest, TBX20 NM_001166220 6 7 35271111 35271192 Gene Specific Sequencing: PCR-based or NGS-based sequencing of entire coding region, intron/exon Low coverage (<20X) regions boundaries of the specified gene GENE TRANSCRIPT EXON CHROM EXON_START EXON_END Variant Specific Analysis: Sanger sequencing following CDC42 NM_001791 6 1 22417920 22418010 PCR amplification of the targeted variant(s) of the CFHR1 NM_002113 1 1 196788974 196789032 specified gene CFHR2 NM_005666 1 1 196913010 196913068 Deletion/Duplication Analysis: Copy number variant CFHR3 NM_021023 4 1 196757345 196757528 analysis of the gene by comparative genomic hybridization CFHR3 NM_021023 5 1 196759174 196759357 CORO1A NM_007074 11 16 30200180 30200285 Results: EFL1 NM_024580 7 15 82530647 82530862 Each test report includes a detailed interpretation of the FANCD2 NM_033084 14 3 10085512 10085548 genetic findings, the clinical significance of the esult,r and FANCD2 NM_033084 17 3 10091057 10091189 specific ecommendationsr for the clinical management and FANCD2 NM_033084 22 3 10106039 10106113 additional testing, if warranted. Results will be reported to IGLL1 NM_152855 2 22 23915723 23915772 the referring physician or health care provider as specified PLEKHM1 NM_014798 2 17 43559802 43559850 on the test requisition form. PLEKHM1 NM_014798 8 17 43527983 43528129 PLEKHM1 NM_014798 9 17 43522835 43523029 Please note: These regions represent the low coverage (<20X) regions identified during our test validation. For specific patient cases, these regions may vary slightly. Turn-Around Time: FBN1 Full Mutation Analysis: 81408 Gene panels: up to 6 weeks LDLR Gene Sequencing: 81406 Individual/custom gene sequencing: up to 6 weeks Marfan Syndrome and MFS Related Disorders Panel: Targeted analysis: up to 2 weeks 81405 x2, 81408 Deletion/Duplication analysis: up to 4 weeks RASopathy/Noonan Spectrum Disorders Panel: 81442 Short QT Syndrome Panel: 81403, 81406, 81479 x2 Thoracic Aortic Aneurysm Panel: 81410 CPT Codes: TTN Full Mutation Analysis: 81479 APOB (R3500Q/R3500W) Sequencing Analysis: 81401 Targeted variant analysis and deletion/duplication: Arrhythmogenic Right Ventricular Cardiomyopathy call for information. (ARVC) Panel, Dilated Cardiomyopathy (DCM) Panel, Please call 1-866-450-4198 for current pricing, insurance Hypertrophic Cardiomyopathy (HCM) Panel, Left preauthorization or with any billing questions. Ventricular Noncompaction (LVNC) Panel, Restrictive Cardiomyopathy (RCM) Panel: 81439 Shipping Instructions: Atrial Fibrillation (A Fib) Panel, Brugada Syndrome Please enclose test requisition with sample. All Panel, Congenital Heart Disease Panel, Heterotaxy information must be completed before sample can Panel, Long QT Syndrome Panel, Pulmonary Arterial be processed. Place samples in styrofoam mailer and ship at room temperature by overnight Hypertension (PAH) Panel: 81443 Federal Express to arrive Monday through Atrioventricular Block (AV Block) Panel: 81404, Saturday. 81405, 81406 Ship to: Comprehensive Arrhythmia Panel: 81413 Laboratory of Genetics and Genomics Catecholaminergic Polymorphic Ventricular 3333 Burnet Avenue NRB 1042 Tachycardia (CPVT) Panel: 81403, 81405, 81408 Cincinnati, OH 45229 Comprehensive Cardiomyopathy Panel: 81439 513-636-4474 Arrythmia Disorders: Panel Name # of Genes Genes Comprehensive Arrhythmia Panel ABCC9, ACTN2, AKAP9, ANK2, ANKRD1, BAG3, CACNA1C, CACNA2D1, 81 CACNB2, CALM1, CALM2, CALM3, CASQ2, CAV3, CDH2, CPT1A, CTNNA3, DES, DSC2, DSG2, DSP, EMD, FLNC, GATA4, GATA5, GATA6, GJA5, GNB5, GPD1L, GYG1, HCN4, JUP, KCNA5, KCND3, KCNE1, KCNE1L, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNK3, KCNQ1, KCNQ3, LDB3, LMNA, MYH6, MYH7, MYL4, NKX2-5, NOS1AP, NPPA, NUP155, PDLIM3, PKP2, PLN, PPA2, PRKAG2, RANGRF, RBM20, RYR2, SCN10A, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SLC25A20, SLMAP, SNTA1, TBX5, TECRL, TGFB3, TMEM43, TNNI3, TNNI3K, TNNT2, TRDN, TRPM4, TTN Atrial Fibrillation (A Fib) Panel 28 ABCC9, CACNB2, GATA4, GATA6, GJA5,